Could initial CT chest manifestation in patients hospitalized with COVID 19 pneumonia predict outcome on short term basis

Chest computed tomography (CT) can be used to monitor the course of the disease or response to therapy. Therefore, our study was designed to identify chest CT manifestations that can predict the outcome of patients on short term follow-up. This was a retrospective study wherein we reviewed chest CT scans of 112 real-time reverse transcription polymerase chain reaction positive patients admitted to our hospital. All 112 patients underwent follow-up chest CT at a time interval of 4 to 42 days. Our study included 83 male and 29 female who were positive for COVID 19 infection and admitted to the hospital with positive chest CT findings. All patients underwent follow-up chest CT, and the outcomes were categorized as resolution, regression, residual fibrosis, progression, or death. These proportions were 5.4%, 48.2%, 24.1%, 14.3%, and 8%, respectively. The only significant factor in determining the complete resolution of chest CT was oligo-segmental affection (P = .0001). The main CT feature that significantly affected the regression of chest CT manifestations was diffuse nodular shadows (P = .039). The CT features noted in patients with residual fibrosis were interstitial thickening, with a P value of .017. The mono-segmental process significantly affected progression (P = .044). The significant factors for fatality were diffuse crazy paving, pleural effusion, and extra-thoracic complications (P = .033, .029, and .007, respectively). The prognostic value of the first admission CT can help assess disease outcomes in the earliest phases of onset. This can improve resource distribution.


Introduction
Since the coronavirus disease 2019 (COVID-19) outbreak started in Wuhan, China, in December 2019 as the first human case infected, the virus has rapidly spread with human-to-human transmission despite imposed precautions and was announced as a pandemic by the WHO Health Organization on March 12, 2020. [1] Chest computed tomography (CT) is an easy, rapid, and noninvasive modality for the diagnosis of pneumonia, with a sensitivity of 98% for the diagnosis of patients with COVID-19 pneumonia. [2] CT chest repetition is allowed in suspected cases with complications; however, in recovering patients, chest CT is not the modality of choice. [3] Chest CT can be used to monitor the course of the disease or the response to therapy. [4] Recent studies have shown that about 94% of COVID 19 pneumonia patients showed lung manifestation at the last scan before discharge, [5] while half of the patients with mild severity COVID 19 pneumonias resolve within 3 weeks. [6] Other modalities are available to assess patients with COVID infection, they have many limitations. For example, chest radiography proved to be of limited value in the diagnosis of early stages, especially in mild disease courses, compared to the intermediate to advanced stages of COVID-19 with features of acute respiratory distress syndrome (ARDS) and follow-up. [7] Benmalek et al [8] reported a higher sensitivity of chest CT than chest radiography in detecting positive cases of COVID pneumonia.
Another modality that could be considered is Chest US; however, it also has limitations in the diagnosis of COVID pneumonia. According to Colombi et al, [9] admission chest CT shows better performance than Lung US for COVID-19 diagnosis at varying disease prevalence. Chest US showed high sensitivity but was not specific for COVID-19.
Patients survived COVID 19 infections either recover completely, develop functional impairment in the form of persistent symptoms, or develop abnormalities after full recovery. [10] In our study, the patient underwent CT at admission with follow-up CT before discharge or to follow-up complications with a time interval of 4 to 42 days (mean 11.60 days ± standard deviation [SD] 7.95). All chest CT manifestations at the time of admission were recorded, and in follow-up CT, we stratified patients with complete resolution, regression, Residual fibrotic pattern, progression, or death. Medicine The aim of our study was to detect chest CT manifestations that can predict the outcome of patients during short-term follow-up. The prognostic value of the first admission CT can help assess disease outcomes in the earliest phases of onset. This can improve resource distribution.

Materials and methods
This was a retrospective study wherein we reviewed the chest CT scans of 112 real-time reverse transcription polymerase chain reaction positive patients at our hospital from April 2021 to December 2021. All patients underwent chest CT at admission, followed by chest CT just before discharge or with the development of complications. The study was approved by the Institutional Ethical committee. The requirement for informed patient consent was waived.

Study design and participants
This retrospective study was approved by the ethics committee of the Ain Shams University. All participants were anonymous. Initial chest CT was performed on the first day of admission. All 112 patients underwent follow-up chest CT with a time interval of 4 to 42 days (mean 11.60 days ± SD 7.95) using the same CT chest scanner and the same protocol. All patients underwent follow-up CT before discharge due to the short hospital stay and the need to confirm complete resolution before being released from the hospital. The remaining patients who had regression or progression, chest CT was performed as part of the follow-up.
All CT images were reviewed by 3 senior cardiothoracic radiologists (with 14, 7, and 6 years of experience in thoracic radiology). The readers independently assessed the CT features using the axial and multiplanar reconstructed images. The predominant CT patterns were as follows: ground-glass opacities, consolidation, halo sign, crazy paving, reticulation, subpleural line, fibrotic strips, presence of nodules, bronchiectasis, pleural effusion, pleural thickening, and Lymph Nodes. Then, lobar affection as multi-segmental, oligo-segmental, or mono-segmental was stratified followed by zonal affection either upper, lower, or diffuse distribution.
CT evidence of residual fibrotic-like changes was defined as the presence of residual reticulation, ground glass, and fibrotic-like changes.
Chest CT manifestations recorded on the first day were compared with the follow-up CT at discharge. The findings affecting the outcome were tabulated, and their significance was calculated. The assessment system was built for future CT chest evaluations at the time of admission for COVID 19 infected patient (Fig. 1).

Imaging protocol
All participants with a positive PCR test for COVID-19 underwent chest CT using a multi-slice 128 CT machine (Optima CT 660; GE, Boston, MA). Axial high-resolution lung tissue cuts were made with a slice thickness of 0.63 cm with and a GAP of 4.38. The axial lung and mediastinal windows were imaged with a slice thickness of 5 mm and a GAP of 0. Coronal and sagittal reconstructions were performed in the lung and mediastinal windows.

Data management and statistical analysis
The collected data were revised, coded, tabulated, and introduced to a PC using the Statistical Package for Social Sciences (IBM SPSS 20.0). Data are presented, and suitable analysis was performed according to the type of data obtained for each parameter.

Descriptive statistics
Mean ± SD and range for parametric numerical data, and median and interquartile range for non-parametric data.

Analytical statistics:
Chi square test was used to examine the relationship between 2 qualitative variables; however, when the expected count was less than 5 in more than 20% of the cells, Fisher's exact test was used. P value: level of significance: P > .05: non-significant; P < .05: significant; P < .01: highly significant.

Results
Our study included 83 male and 29 female who were positive for COVID 19 infection and admitted to the hospital with positive chest CT findings. Their ages ranged from 31 to 60 years as shown ( Table 1).
The positive radiological findings were ground glass opacity in 86.4% of our patients, followed by consolidations in 44.6%, fibrotic strips in 51.8%, reticular pattern in 26.8%, subpleural line in 22.3%, and nodules in 17.9%. The least common findings were the halo sign, which was seen in 17 patients, crazy paving in 6 patients, and reverse halo sign in only5 patients.
Regarding distribution, 81.2% of our study population showed multi-segmental affection, with nearly half of the patients showing diffuse zonal affection, and more than onethird of the patients showed lower zone predominance ( Table 2).
Only 2 patients had other findings not related to COVID 19 infection that including pneumothorax and pneumomediastinum (post-intubation) and sub-pleural calcific nodules.
Complications of COVID 19 were seen as effusion in 5 patients (secondary to on-top bacterial infections) and 1 patient developed pulmonary embolism. Extra thoracic complications included pericardial effusion, hemorrhagic encephalitis, and multi-organ failure ( Table 3).
All patients underwent follow-up CT either before discharge to confirm the resolution of the disease, as part of follow-up, or with development of complications.
We found that 40% of patients admitted with diffuse crazy paving ended by death, which represents a significant factor with a P value of .033. Pleural effusion developed in about 40% of the patients who died and was a significant factor in fatality (P = .029). All patients who developed extrathoracic complications apart from pericardial effusion ended with death, all of which were significant factors (P = .007) ( Table 5). Table 1 Characteristics of the studied patients (n = 112).

Variables
No. %   The total fatality rate in our study was 9 patients, all of whom showed diffuse ground glass opacities, 6 of whom showed diffuse interstitial thickening, mainly sub-pleural with fibrotic strips and sub-pleural lines, 4 patients showed crazy paving at the time of admission, 2 patients showed consolidations mainly peripheral, 3 patients developed effusion, one had cavitation and pulmonary embolism. The cause of death was mainly the development of ARDS, which was seen in 6 out of 9 patients.

Age
The other 3 died of extra-thoracic complications, including hemorrhagic encephalitis and multi-organ failure.
The only significant factor in determining the complete resolution of chest CT was oligo-segmental affection (P = .0001) ( Table 6).
Six of the 112 patients who showed complete resolution of CT after short-term follow-up had sub-pleural ground-glass Table 6 Factors affecting resolution in the studied patients (n = 112).     Table 9 Factors affecting progression in the studied patients (n = 112).  opacity, one showed sub-pleural ground-glass nodules, and one showed Sub-pleural lines associated with sub-pleural groundglass opacities. Patients with regressive chest CT manifestations were more common in the 31 to 40 years group, with a significant P value of .022. The main CT feature that significantly affected the regression of chest CT manifestations was diffuse nodular shadows (P = .039) ( Table 7).

Variables
Of the 54 patients with a regressive course, 49 showed ground glassing, 24showed consolidation, 29 had fibrotic strips, 13 had interstitial thickening, and 12 showed subpleural lines.
Forty-six patients showed multi-segmental affection, 6 oligo-segmental affection, and 2 had mono-segmental affection on chest CT. The other chest CT finding noted was mild effusion in 2 patients.  Only 1 patient had an extra thoracic complication, pericardial effusion, which was resolved on follow-up CT.
The CT features noted in patients with residual fibrosis were interstitial thickening, which was observed in 40% of patients (P = .017) ( Table 8).
A total of 27 patients showed residual fibrosis, 20 out of the 27 showed ground glass and 13 out 0f 27 showed consolidations with different distributions. Eighteen patients had fibrotic strips, eight had a subpleural line, three had nodules, and only 1 patient had a crazy paving pattern at the time of admission. Nearly all patients showed multi-segmental affection, except for 1 patient who had oligo-segmental affection. Only 1 patient developed pneumothorax and pneumomediastinum as post-intubation complications.
All patients who showed early Chest CT progressive features after a short-term follow-up finally resolved clinically and were discharged with clinical improvement; however, these patients were not followed up in our study. We found that the mono-segmental process significantly affected progression (P = .044) ( Table 9).
Sixteen patients showed progressive chest CT features, 14 out of 16 showed ground glassing opacities, 8 patients showed consolidations, 6/16 showed fibrotic strips, 3 had interstitial marking, 2 showed sub-pleural line, 2 showed halo sign, 2 had nodules and only 1 patient showed central crazy-paving changes. The main distribution was multisegmental, observed in 10 patients. The zonal distribution was equal between diffuse and lower zone affection. None of these patients had pleural effusion, lymph node involvement, or extra-thoracic complications.

Discussion
In our study, we tried to assess the significance and prognostic value of each chest CT characteristic at the short-term follow-up of patients diagnosed with COVID 19 infections and showed positive results in the initial chest CT at the time of admission.
Laino et al [11] found that the CT scan sensitivity as a prognostic factor was high during the first 2 to 3 weeks after symptom onset. However, Li et al demonstrated that CT prognosis was more significant if it was performed within 6 days of symptom onset. They found that the main prognostic characteristic was in the period of 6 to 10 days. In our study, the time interval was 4 to 42 days.
Liu et al, [12] who followed up patients admitted to their hospital and diagnosed with COVID 19 infection, found that complete resolution was significantly higher in patients younger than 44 years. In our study, no association was found between the age of the patients and complete resolution; however, it was seen as a significant factor in patients with regressive CT chest features (the patient age was between 31 and 40 years old).
Another study by Meiler et al [13] found that only 1 chest CT feature associated with favorable outcome was unilateral distribution, which was comparable to our study, which proved oligo-segmental affection as the main significant factor for resolution (Figs. 2 and 3).
We also proved that diffuse nodular shadows were another significant factor in determining regression, with a P value of .047. This could be attributed to the extent of parenchymal involvement, as nodular shadows could represent an early manifestation of COVID-19 pneumonia, so early less parenchymal involvement could lead to regression of the disease process (Fig. 4).
The main significant feature that showed a significant P value in patients who died was diffuse crazy paving followed by pleural effusion, considering both as poor prognostic factors. This agrees with the findings of Erturk et al, [14] who found that the significant prognostic factors associated with ICU admission were crazy paving and enlargement of the mediastinal hilar node. Also, Parry eta al, [15] divided the patient into either stable or non-stable. They found that bilateral central involvement was more significant in unstable patients, and 70% of clinically unstable patients showed a crazy paving pattern.
Laino et al found that more severe disease was seen in patients with bilateral multi-lobar affection and the association of ground glassing with consolidation. This was explained by Meiler et al, who proved in a multivariable study that increased the extent of disease seen as pleural effusion, crazy paving, and geographic shape of opacifications, which are features of ARDS and can be seen in severe cases of COVID-19 pneumonia and poor prognosis (Fig. 5).
Only 16 patients showed progression of their chest CT after short-term follow-up, yet all had a prolonged hospital stay followed by clinical resolution and discharge (Fig. 6). In our study, the main significant factor associated with disease progression was upper lobe involvement (P = .044). early progression, followed by resolution and discharge, has not been discussed in   previous studies. Monosegmental affection could be added to favorable outcomes even if patients show short-term CT progression, as it will be followed by clinical regression of symptoms and resolution.
Residual interstitial patterns were observed in 27 of 112 patients in the form of residual reticulation, ground glassing, and fibrotic-like changes. A significant factor was interstitial thickening noted at the time of admission (P = .017) (Fig. 7).
The main drawbacks in our study were: first, chest CT could not be repeated in patient with progressive CT course when they showed regression or resolution of clinical symptoms. Second, patients with residual fibrotic CT features should undergo intermediate-or long-term follow-up. And finally the study need to be multicenter assessment with longer follow up and larger number of patients.
In conclusion initial CT at the time of admission can help predict follow-up CT outcomes. As discussed, complete resolution was significantly associated with oligo-segmental affection, and a regressive course of CT features was observed in patients who developed CT nodular shadows. However, significant fatality was observed in patients who developed ARDS and in patients with pleural effusion.